Prediction of hydrogen-bonding networks around tyrosyl radical in P. eryngii versatile peroxidase W164Y variants: a QM/MM MD study

Abstract

Quantum mechanics/molecular mechanics molecular dynamics simulations have been used to predict the hydrogen-bonding networks in the active site of three double variants of Pleurotus eryngii versatile peroxidase containing a redox-active tyrosine in place of a tryptophan residue in position 164. The adopted computational strategy has proved to be adequate to correctly reproduce the hydrogen-bonding environment of tyrosyl radical (Tyr^√) in the single W164Y variant of the enzyme that has been directly identified by electron paramagnetic resonance spectroscopy. In this study, we have investigated the effect of the mutation of a specific amino acid in the local environment of tyrosine 164. We show that the substitution of arginine 257 with a glutamic acid, a leucine or an alanine residue is able to induce the stabilisation of different hydrogen-bonding networks involving Tyr^√ that can potentially affect its physico-chemical properties.

Keywords::

• tyrosyl radical
• versatile peroxidase
• DFT
• molecular dynamics
• electron transfer

Acknowledgements

We acknowledge the CINECA award no. HP10CXBWGO for the availability of high-performance computing resources and support. This work was supported by the Italian MIUR PRIN 2009 project no. 2009STNWX3_001.

Notes

^1. Please note that these results are obtained under the assumption that the protein backbone remains the same as in W164Y variant.